JNK信号通路在大鼠肝再生及肝硬化的细胞增殖和凋亡中作用的比较  

Comparative analysis of the role of JNK signaling pathway in cell proliferation and apoptosis of rat liver regeneration and cirrhosis

作　　者：冯利娟[1,2] 段丽娟[1,2] 张瑞刚[1,2] 张新胜[1] 徐存拴 

机构地区：[1]河南师范大学生命科学学院,河南新乡453007 [2]河南省-科技部共建细胞分化调控国家重点实验室培育基地,河南新乡453007

出　　处：《解剖学报》2012年第3期352-358,共7页Acta Anatomica Sinica

基　　金：国家973项目前期研究专项基金资助项目(2010CB534905)

摘　　要：目的从基因转录水平了解JNK信号通路在大鼠肝再生(LR)和肝硬化(LC)中的作用异同。方法采用2/3部分肝切除手术制备大鼠肝再生模型,以腹腔注射CCl4中性菜籽油溶液法建立大鼠肝硬化模型,采用大鼠Genome 230 2.0芯片检测不同时间点再生肝和肝硬化组织中JNK信号通路的基因表达谱,用生物信息学和系统生物学等方法分析基因表达谱预示的增殖和凋亡活动。结果 JNK信号通路涉及302个基因和42条途径,大鼠Genome 230 2.0芯片含上述基因中的240个基因,其中,79个基因发生有意义表达变化,涉及LR的52个基因,LC的5个基因,有22个基因与两者相关。在大鼠LR启动阶段,途径1和16促进细胞增殖及途径22～33促进细胞凋亡作用强于对照;在进展阶段,途径1～17、34和35促进细胞增殖及途径22～33促进细胞凋亡作用强于对照,途径37～41抑制细胞凋亡作用弱于对照;在终止阶段,途径37、39、41和42诱导细胞凋亡作用弱于对照,同时,尚未发现途径18～21和36参与大鼠LR。而在LC发生中,JNK信号通路中的这些途径与对照相比均无显著差异。结论 JNK信号通路的37条途径调控大鼠肝再生的细胞增殖和凋亡,对大鼠肝硬化的调控作用则不显著。Objective JNK signaling pathway regulates some physiological activities, including inflammation, cell proliferation, differentiation, apoptosis and stress response. The study was to compare the role of JNK signaling pathway in rat liver regeneration （LR） and in rat liver cirrhosis （LC） at the gene transcription level. Methods The rat LR model was established by 2/3 partial hepatectomy（ PH）, and the LC model was induced by intraperitoneal injection of CC14 and colza oil. Rat Genome 230 2.0 array was used to detect gene expression profiles of JNK signaling pathway-related genes , and bioinformatics and systems biology methods were used to analyze the physical activities which were predicted by the expression profiles. Results JNK signaling pathway includes 302 genes and 42 branches. Of them, 240 genes were contained in Rat Genome 230 2. 0 array, including 79 significantly expressed genes. In detail, 52 genes were the LR- specific, 5 genes the LC-specific, and 22 genes the common. The cell proliferation-promoting effect of paths 1 and 16 and the cell apoptosis-promoting effect of paths 22-33 became stronger at the priming phase of LR than in control; the cell proliferation-promoting effect of paths 1-17, 34 and 35 and ceil apoptosis-promoting effect of paths 22-33 was enhanced at the progressing phase of LR, while the cell apoptosis-inhibiting effect of paths 37-41 and the cell apoptosis-inducing effect of paths 37, 39, 41 and 42 was weakened at the terminal phase. Paths 18-21 and 36 were found not to be involved in rat LR. JNK signaling pathway of LC worked as that of the control did. Conclusion Thirty-seven branches of the JNK signaling pathway regulat cell proliferation and apoptosis in rat LR, but may not be significantly involved in rat LC.

关 键 词：肝再生 肝硬化 JNK信号通路 GENOME 230 2.0芯片检测 基因协同作用 大鼠 

分 类 号：Q257[生物学—细胞生物学]